Tau protein plays a crucial role in human brain by regulating the assembly and structural stability of microtubules in neurons. Various malfunctions of tau are responsible for several neurodegenerative diseases (tauopathies) such as Parkinson’s disease or Alzheimer’s disease. Each tauopathy is characterized by unique neuropathological changes, like the formation of neurofibrillary tangles, composed of aggregated tau and other proteins. The study of tau folds is further complicated by the post-translational modifications tau undergoes. However, current experimental techniques barely provide insights into the mechanism of tau aggregation. Therefore, the student will employ various computational methods (atomistic or coarse-grained Molecular Dynamics) to explore the aggregation of unmodified or modified tau protein and establish a computational approach to shed light on their aggregation mechanisms. The impact of selected mutations or phosphorylation on the Tau fibrils stability will be explored by free energy calculations.

Keywords: computational simulations, tau protein, phosphorylation, neurodegenerative diseases, free energy calculations